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Multiple Amino Acid Poly Ester-Amide (PEA-AA) Polymer Coating Significantly Reduces Suture Associated Inflammation
Karina A. Hernandez, D.O.1, Tatiana Boyko, MD1, Rachel Campbell, MD1, Andrew Weinstein, MD1, Alice Harper, BA1, Chih-Chang Chu, PhD2, Jason A. Spector, MD, FACS1.
1Weill Cornell Medical College, New York, NY, USA, 2Cornell University, Ithaca, NY, USA.
BACKGROUND: Although ubiquitous and irreplaceable in the practice of surgery, sutures themselves can cause morbidity. The inflammatory reaction that is elicited after suture implantation can lead to complications such as suture “spitting”, abscess formation, keloids, hypertrophic scarring, and granuloma formation. We have developed two novel amino acid conjugated Poly Ester Amide (PEA-AA) coatings, 8-Phe-4-PEA (Phe-PEA) and [2-Arg-4]-[2-Phe-4]-PEA (Arg-Phe-PEA) which have previously been shown to be biocompatible and non-toxic, conducive to cell adhesion and growth and may be degraded by endogenous enzymes all while minimizing activation of macrophages. We thus hypothesized that these materials would decrease the inflammation associated with Silk and Plain-gut sutures, two of the more “reactive” sutures available. We investigated the inflammation elicited by the Phe-PEA and Arg-Phe-PEA coatings when compared to non-coated control sutures.
METHODS: C57BL/6 mice underwent Silk or Plain-gut suture implantation in the bilateral gluteal muscles: either Phe-PEA or Arg-Phe-PEA coated 3-0 Silk or 3-0 Plain-gut suture was implanted in the right and a non-coated, control suture in the left. Animals were sacrificed after 3, 7, 14 and 28 days. The gluteal muscles were harvested and the area of inflammation surrounding each suture was quantified and compared between experimental groups and controls. The percent reduction of inflammation in coated sutures was calculated when compared to non-coated controls.
RESULTS: Both PEA-AA coatings resulted in consistent reduction of inflammation when compared to controls. Phe-PEA coating decreased inflammation at all time points in the Silk group. This difference was statistically significant after 3 days (67.8%±17.4% [p=0.0014]), 7 days (51.6%±7.2% [p<0.001]) and after 28 days (37.3%±8.3% [p=0.0004]). In the plain-gut group, the Phe-PEA coated sutures showed a statistically significant decrease in inflammation across all time points (54.1%±8.3% after 3 days [p<0.0001], 41.4%±3.9% after 7 days [p<0.0001], 71.5%±8.1% after 14 days [p<0.0001], 78.4%±8.5% after 28 days [p<0.0001]). Statistically significant percent reduction of inflammation was also observed at 3 days (61.3%+/-9.4, p<0.0001), 7 days (44.7%+/-4.7, p<0.0001), and 28 days (38.3%+/-6.8, p<0.0001) for Silk Arg-Phe-PEA coated sutures and at 3 days (37.4 +/-8.3, p=0.0004), 7 days (55.0%+/-7.8, p<0.0001), 14 days (46.0%+/-4.6, p<0.0001) and 28 days (59.0%+/-7.9, p<0.0001) for Plain-gut Arg-Phe-PEA coated sutures. There was no statistically significant difference seen in the percent reduction of inflammation between the Phe-PEA and Arg-Phe-PEA coatings.
CONCLUSIONS: Our novel multiple amino acid based coatings prove to significantly decrease the local immune response to typically inflammatory Plain-gut and Silk sutures. The reduction in inflammation induced by Arg-Phe-PEA was not different than that seen with the Phe-PEA coating. Although further studies are warranted before clinical application is possible, the PEA-AA coating is a simple and promising means of decreasing complications that are associated with suture induced inflammation.
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